Oral dissolvable film that includes plant extract

ABSTRACT

Films (ODFs) that include botanical extract are provided, as well as methods of making and using the same.

PRIORITY APPLICATION

This application claims the benefit of priority to U.S. ProvisionalPatent Application Ser. No. 62/029,757, filed on Jul. 28, 2014, whichapplication is incorporated herein by reference in its entirety.

BACKGROUND

Raw Botanical Extracts (RBEs) of cannabinoids, in their concentratedform, are typically viscous oils at room temperature and pressure. Theseoils contain cannabinoids, plant waxes, plant lipids, and sometimesplant pigments such as chlorophylls. These RBEs present some problemsfor incorporation into ODFs when treated like dry, solid, crystallineactive pharmaceutical ingredients (APIs). Direct incorporation in aslurry typically results in sticky mixtures that do not form viable ODFshaving desirable properties like being dry to touch, easily handled andpackaged, and/or easily consumed. As such, what is needed is a way toincorporate RBEs into ODFs that are dry to touch, easily handled andpackaged, and/or easily consumed. What is further needed is for the ODFto be configured and formulated for the release of the active ingredientin the RBEs, in a variety of profiles (e.g., immediate release (IR),sustained release (SR), delayed release (DR), modified release (MR),extended release (XR), and controlled release (CR)).

SUMMARY

In various embodiments, the thin film described herein includes thepotential to improve the onset of action, lower the dosing, and enhancethe efficacy and safety profile of the active ingredient. All tabletdosage forms, softgels, and liquid formulations primarily enter theblood stream via the gastrointestinal tract, which subjects the drug todegradation from stomach acid, bile, digestive enzymes, and othereffects including first-pass liver metabolism. As a result, suchformulations often require higher doses and generally have a delayedonset of action. Conversely, in various embodiments, the thin filmdescribed herein can avoid these issues and yield quicker onsets ofaction at lower doses.

In various embodiments, the thin film described herein provides for astable, durable and quick dissolving dosage form.

In various embodiments, the thin film described herein enables suitabledosing accuracy, since every strip is manufactured to contain arelatively precise amount of the active ingredient.

In various embodiments, the thin film described herein not only ensuresmore accurate administration of active ingredients but also can improvecompliance due to the intuitive nature of the dosage form and itsinherent ease of administration. These properties are especiallybeneficial for pediatric, geriatric, and neurodegenerative diseasepatients where proper and complete dosing can be difficult.

In various embodiments, the thin film described herein possesses theability to dissolve rapidly without the need for water, which providesan alternative to patients with swallowing disorders and to patientssuffering from nausea, such as those patients receiving chemotherapy.

In various embodiments, the thin film drug delivery has the potential toallow the development of sensitive active ingredient targets that mayotherwise not be possible in tablet or liquid formulations.

Sublingual film delivers a convenient, quick-dissolving therapeutic dosecontained within an abuse-deterrent film matrix that cannot be crushedor injected by patients, and rapidly absorbs under the tongue to ensurecompliance.

In various embodiments, the thin film described herein can bemanufactured to include a relatively high load of active ingredient. Forexample, the active ingredient can be present in about 25-40 wt. %. Sucha relatively high load of active ingredient can be advantageous when thedelivery of a high load of active ingredient is needed, especially whenconventional thin films cannot be readily manufactured to include such ahigh load of the active ingredient.

In various embodiments, the thin film described herein incorporate RBEsinto an ODF, such that the ODF is dry to touch.

In various embodiments, the thin film described herein incorporate RBEsinto an ODF, such that the ODF is easily handled and packaged.

In various embodiments, the thin film described herein incorporate RBEsinto an ODF, such that the ODF is easily consumed.

In various embodiments, the thin film described herein is configured andformulated for the immediate release (IR) of the active ingredient inthe RBEs.

In various embodiments, the thin film described herein is configured andformulated for the sustained release (SR) of the active ingredient inthe RBEs.

In various embodiments, the thin film described herein is configured andformulated for the delayed release (DR) of the active ingredient in theRBEs.

In various embodiments, the thin film described herein is configured andformulated for the modified release (MR) of the active ingredient in theRBEs.

In various embodiments, the thin film described herein is configured andformulated for the extended release (XR) of the active ingredient in theRBEs.

In various embodiments, the thin film described herein is configured andformulated for controlled release (CR) of the active ingredient in theRBEs.

In various embodiments, the thin film described herein is configured andformulated for the release of the active ingredient in the RBEs, in avariety of profiles (e.g., immediate release (IR), sustained release(SR), delayed release (DR), modified release (MR), extended release(XR), and controlled release (CR)).

The present invention provides a thin film (e.g., an oral dissolvablefilm) that includes: (a) solvent, (b) binder, (c) optionally a lipid,(d) emulsifier, (e) botanical extract, (f) optionally a doughconditioner, (g) optionally a flavoring agent, (h) optionally asweetener, (i) optionally a dye or pigment, (j) a powder coating on atleast one external surface, and (k) optionally a preservative. Thebotanical extract can optionally be at least partially encapsulated bythe lipid, when present.

The present invention also provides a thin film (e.g., an oraldissolvable film) that includes: (a) about 2-24 wt. % solvent, (b) about40-50 wt. % binder, (c) about 0-22 wt. % wt. % lipid, (d) about 3-22 wt.% emulsifier, (e) up to about 65 wt. % botanical extract, (f) about 0-15wt. % wt. % dough conditioner, (g) about 0-10 wt. % flavoring agent, (h)about 0-40 wt. % sweetener, (i) about 0-1.0 wt. % dye or pigment, (j)about 0-20 wt. % powder coating on at least one external surface, and(k) about 0-0.1 wt. % preservative. The botanical extract can optionallybe at least partially encapsulated by the lipid, when present.

The present invention also provides an orally dissolving film thatincludes: (a) solvent that includes water, (b) binder that includespectin, (c) optionally a lipid that includes at least one of deodorizedcocoa butter oil, fruit seed oil, and vegetable based oil, (d)emulsifier that includes at least one of glycerin, ethoxylatedmonoglycerides, and ethoxylated diglycerides, (e) botanical extract, (f)flavoring agent that includes mint flavoring, (g) sweetener thatincludes at least one of sucralose and acesulfame potassium, (h) dye orpigment that includes at least one of FD&C red. FD&C blue, and FD&Cyellow, (i) a powder coating on at least one external surface, thatincludes at least one of talc, microcrystalline cellulose, mintflavoring, sucralose, acesulfame potassium, and tapioca starch, and (j)optionally a preservative that includes at least one of sodium benzoate,methyl paraben, propyl paraben, and sodium sorbate. The botanicalextract can optionally be at least partially encapsulated by the lipid,when present.

The present invention also provides an orally dissolving film thatincludes: (a) about 2-24 wt. % solvent that includes water, (b) about4-50 wt. % binder that includes pectin, (c) about 0-22 wt. % lipid thatincludes at least one of deodorized cocoa butter oil, fruit seed oil,and vegetable based oil, (d) about 3-22 wt. % emulsifier that includesat least one of glycerin, ethoxylated monoglycerides, and ethoxylateddiglycerides, (e) up to about 65 wt. % botanical extract, (f) about 0-10wt. % flavoring agent that includes mint flavoring, (g) about 1-40 wt. %sweetener that includes at least one of sucralose and acesulfamepotassium, (h) about 0-1.0 wt. % dye or pigment that includes at leastone of FD&C red, FD&C blue, and FD&C yellow, (i) about 0-20 wt. % powdercoating on at least one external surface, that includes at least one oftalc, microcrystalline cellulose, mint flavoring, sucralose, acesulfamepotassium, and tapioca starch, and (j) about 0-0.1 wt. % preservativethat includes at least one of sodium benzoate, methyl paraben, propylparaben, and sodium sorbate. The botanical extract can optionally be atleast partially encapsulated by the lipid, when present.

The present invention also provides a method of preparing a thin film(e.g., an oral dissolvable film). The method includes: (a) contacting(e.g., mixing) a lipid, emulsifier, and solvent to provide a uniformfirst mixture; (b) contacting an active ingredient (e.g., botanicalextract) with the uniform first mixture to provide a thickened secondmixture; (c) contacting a binder with the thickened second mixture toprovide a slurry; and (d) hot extruding, casting, and condensing theslurry to provide the thin film; or cooling, shearing, mixing, casting,and condensing the slurry to provide the thin film.

The present invention also provides a system that includes: (a) multiplethin films (e.g., multiple oral dissolvable films), each in directcontact with at least one other thin film, and each independentlydescribed herein; (b) packaging material enclosing the multiple thinfilms; and (c) printed indicia located on the packaging material;wherein the multiple thin films do not readily stick to another.

BRIEF DESCRIPTION OF THE FIGURES

In the drawings, which are not necessarily drawn to scale, like numeralsdescribe substantially similar components throughout the several views.Like numerals having different letter suffixes represent differentinstances of substantially similar components. The drawings illustrategenerally, by way of example, but not by way of limitation, variousembodiments discussed in the present document.

FIG. 1 illustrates a method of preparing an oral film, in variousembodiments.

FIG. 2 illustrates a SEM micrograph of a multilamellar liposomestructure made up of a set of concentric liposomal spheres.

FIG. 3 illustrates a variety of unilamellar and multilamellar liposomalstructures.

FIG. 4 illustrates a diagrammatic representation of a unilamellarliposome.

DETAILED DESCRIPTION

Reference will now be made in detail to certain claims of the invention,examples of which are illustrated in the accompanying drawings. Whilethe invention will be described in conjunction with the enumeratedclaims, it will be understood that they are not intended to limit thoseclaims. On the contrary, the invention is intended to cover allalternatives, modifications, and equivalents, which can be includedwithin the scope of the invention as defined by the claims.

References in the specification to “one embodiment,” “an embodiment.”“an example embodiment,” and the like, indicate that the embodimentdescribed can include a particular feature, structure, orcharacteristic, but every embodiment may not necessarily include theparticular feature, structure, or characteristic. Moreover, such phrasesare not necessarily referring to the same embodiment. Further, when aparticular feature, structure, or characteristic is described inconnection with an embodiment, it is submitted that it is within theknowledge of one of ordinary skill in the art to affect such feature,structure, or characteristic in connection with other embodimentswhether or not explicitly described.

Values expressed in a range format should be interpreted in a flexiblemanner to include not only the numerical values explicitly recited asthe limits of the range, but also to include all the individualnumerical values or sub-ranges encompassed within that range as if eachnumerical value and sub-range is explicitly recited. For example, arange of “about 0.1% to about 5%” or “about 0.1% to 5%” should beinterpreted to include not just about 0.1% to about 5%, but also theindividual values (e.g., 1%, 2%, 3%, and 4%) and the sub-ranges (e.g.,0.1% to 0.5%, 1.1% to 2.2%, 3.3% to 4.4%) within the indicated range.

In this document, the terms “a,” “an,” or “the” are used to include oneor more than one unless the context clearly dictates otherwise. The term“or” is used to refer to a nonexclusive “or” unless otherwise indicated.In addition, it is to be understood that the phraseology or terminologyemployed herein, and not otherwise defined, is for the purpose ofdescription only and not of limitation. Any use of section headings isintended to aid reading of the document and is not to be interpreted aslimiting; information that is relevant to a section heading may occurwithin or outside of that particular section. Furthermore, allpublications, patents, and patent documents referred to in this documentare incorporated by reference herein in their entirety, as thoughindividually incorporated by reference. In the event of inconsistentusages between this document and those documents so incorporated byreference, the usage in the incorporated reference should be consideredsupplementary to that of this document; for irreconcilableinconsistencies, the usage in this document controls.

In the methods of manufacturing described herein, the steps can becarried out in any order without departing from the principles of theinvention, except when a temporal or operational sequence is explicitlyrecited.

Furthermore, specified steps can be carried out concurrently unlessexplicit claim language recites that they be carried out separately. Forexample, a claimed step of doing X and a claimed step of doing Y can beconducted simultaneously within a single operation, and the resultingprocess will fall within the literal scope of the claimed process.

The term “about” as used herein can allow for a degree of variability ina value or range, for example, within 10%, within 5%, or within 1% of astated value or of a stated limit of a range. When a range or a list ofsequential values is given, unless otherwise specified any value withinthe range or any value between the given sequential values is alsodisclosed.

The term “substantially” as used herein refers to a majority of, ormostly, as in at least about 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%,98%, 99%, 99.5%, 99.9%, 99.99%, or at least about 99.999% or more.

“Oral thin film,” “OTF,” “oral dissolving film,” “oral dissolvablefilm,” “oral drug strip” or “oral strip” refers to a product used toadminister active ingredients via absorption in the mouth (buccally orsublingually), the stomach (gastrically), and/or via the smallintestines (enterically). The OTF is edible and pharmaceuticallyacceptable. A film is prepared typically using hydrophilic polymers thatrapidly dissolves on the tongue or buccal cavity, delivering the activeingredient to the systemic circulation via dissolution when contact withliquid is made. The OTF (or more appropriately “thin film” or “TF”) canalso be used to adhere to mucosal tissue (e.g., at least one of mouth,nose, eye, vagina, and rectum), thereby locally delivering the activeingredient. As such, it is appreciated that those of skill in the artunderstand that reference to a thin film for use with mucosal tissue,such as nose, eye, vagina, and rectum, as an “oral thin film” or OTF isappropriate and acceptable.

The thin film is administered to a patient suffering from a disease ordisorder in which the active ingredient (located within the thin film)is believed to treat such disease or disorder. As used herein, the term“treat” includes treating the pathology, delaying the onset of thepathology, slowing the progression of the pathology, and/or to reduce oralleviate at least one of the symptoms of the pathology.

The substances can be selected in an amount such that a desireddissolution rate can be targeted. Upon contact with mucosal tissue(including, e.g., oral mucosa) the TF will completely dissolve withinthe desired period of time. The period of time will vary but inreference to the oral cavity, the period of time will typically bewithin about 30-300 seconds.

“Multiple” refers to two or more (e.g., 2, 3, 4, 5, 6, etc.).

“Solvent” refers to a substance capable of dissolving another substance(a solute), resulting in a solution. When one substance is dissolvedinto another, a solution is formed. This is opposed to the situationwhen the compounds are insoluble like sand in water. In solution, all ofthe ingredients are uniformly distributed at a molecular level and noresidue remains. The mixing is referred to as miscibility, whereas theability to dissolve one compound into another is known as solubility.However, in addition to mixing, both substances in the solution interactwith each other. When something is dissolved, molecules of the solventarrange themselves around molecules of the solute. Heat is involved andentropy is increased making the solution more thermodynamically stablethan the solute alone. This arrangement is mediated by the respectivechemical properties of the solvent and solute, such as hydrogen bonding,dipole moment and polarizability.

In particular reference to the thin films described herein, the solventwill typically dissolve, but may also suspend, the active ingredient andother substances present in the OTF. During the condensing step, much(if not all) of the solvent can be removed. However, any solventremaining will become an integral part of the OTF.

“Binder” refers to any material or substance that holds or draws othermaterials together to form a cohesive whole. Liquid binders are added toa dry substance in order to draw it together in such a way that itmaintains a uniform consistency. The binder can also add mucoadhesion tothe OTF.

The thin film described herein can optionally further include amucoadhesive agent. The mucoadhesive agent, when placed in the oralcavity in contact with the mucosa therein, adheres to the mucosa. Themucoadhesive agent is especially effective in transmucosal delivery ofthe active ingredient, as the mucoadhesive agent permits a close andextended contact of the composition with the mucosal surface bypromoting adherence of the composition or drug to the mucosa, andfacilitates the release of the active ingredient from the composition.The mucoadhesive agent can be a polymeric compound, such as a cellulosederivative but it may be also a natural gum, alginate, pectin, or suchsimilar polymer. The concentration of the mucoadhesive agent in thecoating, such as a powder matrix coating, may be adjusted to vary thelength of time that the film adheres to the mucosa or to vary theadhesive forces generated between the film and mucosa. The mucoadhesiveagent may adhere to oral mucosa or to mucosa or tissue in other parts ofthe body, including the mouth, nose, eyes, vagina, and rectum.Mucoadhesive agents include, e.g., carboxymethylcellulose, polyvinylalcohol, polyvinyl pyrrolidone (povidone), sodium alginate, methylcellulose, hydroxyl propyl cellulose, hydroxypropylmethyl cellulose,polyethylene glycols, carbopol, polycarbophil, carboxyvinyl copolymers,propylene glycol alginate, alginic acid, methyl methacrylate copolymers,tragacanth gum, guar gum, karaya gum, ethylene vinyl acetate,dimenthylpolysiloxanes, polyoxyalkylene block copolymers, pectin,chitosan, carrageenan, xanthan gum, gellan gum, locust bean gum, andhydroxyethylmethacrylate copolymers.

“Lipid” refers to a group of naturally occurring molecules that includefats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E,and K), monoglycerides, diglycerides, triglycerides, phospholipids, andothers. The compounds are hydrophobic or amphiphilic small molecules.The amphiphilic nature of some lipids allows them to form structuressuch as vesicles, liposomes, or membranes in an aqueous environment.Biological lipids originate entirely or in part from two distinct typesof biochemical subunits or “building-blocks”: ketoacyl and isoprenegroups. Using this approach, lipids may be divided into eightcategories: fatty acids, glycerolipids, glycerophospholipids,sphingolipids, saccharolipids, and polyketides (derived fromcondensation of ketoacyl subunits); and sterol lipids and prenol lipids(derived from condensation of isoprene subunits).

Although the term lipid is sometimes used as a synonym for fats, fatsare a subgroup of lipids called triglycerides. Lipids also encompassmolecules such as fatty acids and their derivatives (including tri-,di-, monoglycerides, and phospholipids), as well as othersterol-containing metabolites such as cholesterol.

In particular reference to the thin films described herein, the lipidsfacilitate for the formation of liposomes and micelles.

Liposomes are spherical, lipid bilayer vesicles made from amphiphiliclipids. Typically these are phospholipids that are comprised of aglycerin core with two fatty acid esters, and a phosphate group bound toan additional polar group. These phospholipids thus have two lipophilictails and a single hydrophilic head. Single fatty acid chains with asingle hydrophilic head, like typical soap and detergent molecules, willpreferentially form unilayer micelles and not bilayer liposomalstructures.

Liposomes can be unilamellar, with a single lipid bilayer making asingle sphere. They can also form various multilamellar structures.Multilamellar structures can be concentric spheres, or a spherecontaining multiple unilamellar spheres within. All combinations of theabove have been documented.

FIG. 2 is a SEM micrograph of a multilamellar liposome structure made upof a set of concentric liposomal spheres.

FIG. 3 illustrates a variety of unilamellar and multilamellar liposomalstructures.

FIG. 4 is a diagrammatic representation of a unilamellar liposome. Notethat as the distance from the center of the liposome increases, thedensity of the atoms decreases. This leads to tight grouping of thepolar heads on the interior surface of the lipid bilayer and a loosergrouping of polar heads and tails on the outer surface. The addition ofnon-polar lipids, like triacyl glycerides (standard fats), cholesterol,or tocopherol, can stabilize the bilayer structure by filling in gapsthat the amphiphilic lipids by themselves cannot easily fill.

The interior aqueous capsule in the center of a unilamellar liposome cancontain water—as well as water soluble atoms or molecules. Likewise, theaqueous layers between the lipid bilayers of a multilamellar liposomestructure can contain the same water soluble atoms or molecules as thecenter capsule. The interstitial aqueous environment exterior to theliposomes can contain the same or different aqueous solutions.

The interior of the lipid bilayer is an environment that acts as anorganic solvent, and it will hold lipophilic molecules in solutionwithin the layer. Thus, liposomes contain both lipophilic andhydrophilic solvation environments and can act as carriers of variousaqueous and organic molecules.

Liposomes in close proximity to one another can merge to form largerliposome structures. When the interstitial aqueous phase is partially orcompletely evaporated, liposomes will necessarily come into very closecontact with each other. Adding heat can make a liposome's membrane lessrigid and more apt to merge with neighboring liposomes.

Liposomes will form when amphiphilic phospholipids are high-shearstirred in an aqueous environment. If fats or other organic materialsare included in the process, then they be-come part of the lipidbilayers that make up the liposome's bilayer membrane. Materialdissolved in the aqueous phase will become incorporated into the aqueousphases of the liposomal structures as well.

High shear mixing yields predominantly unilamellar liposomes. Low shearyields various combinations of unilamellar and multilamellar liposomalstructures.

“Encapsulated” refers to the enclosure of a first compound (e.g., activeingredient) by a second compound (e.g., lipid). As described herein, thesecond compound (e.g., lipid) can encapsulate the first compound (e.g.,active ingredient) by the formation of liposomes and/or micelles.

“Emulsifier” refers to a substance capable of forming or promoting anemulsion. An emulsion is a mixture of two or more liquids that arenormally immiscible (nonmixable or unblendable). Emulsions are part of amore general class of two-phase systems of matter called colloids.Although the terms colloid and emulsion are sometimes usedinterchangeably, emulsion should be used when both the dispersed and thecontinuous phase are liquids. In an emulsion, one liquid (the dispersedphase) is dispersed in the other (the continuous phase). Examples ofemulsions include vinaigrettes, milk, mayonnaise, and some cuttingfluids for metal working. The photo-sensitive side of photographic filmis an example of a colloid.

In particular reference to the thin films described herein, theemulsifier promotes the separation of phases (e.g., aqueous and lipids),while allowing them to be mixed.

“Active ingredient” refers to botanical extracts of plant matter(alternatively referred to as “raw botanical extracts (RBEs)” or “rawbotanical extracts (RBEs) of cannabinoids”). The thin film can beadministered, e.g., to a human patient in need of a treatment of adisease or disorder by the administration of the active ingredient(botanical extract). The botanical extract can include kavalactones,tetrahydrocannabinols (THCs) (the isomers of tetrahydrocannabinol),cannabidiol (CBD), and/or cannabinoids. For example, the kava plant willtypically include the active ingredients kavalactones. Likewise, thecannabis plant will typically include the active ingredientstetrahydrocannabinols (THCs) and cannabidiol (CBD).

The phrase “pharmaceutically acceptable” refers to those compounds,materials, compositions, and/or dosage forms that are, within the scopeof sound medical judgment, suitable for use in contact with the tissuesof human beings and animals without excessive toxicity, irritation,allergic response, or other problems or complications commensurate witha reasonable benefit/risk ratio.

The term “botanical extract” or “raw botanical extract (RBE)” refers toa concentrate of plant tissue (e.g., cannabis or kava), typically aviscous oil at ambient temperature and standard pressure. The plant canbe cannabis, such that the RBE can be a “botanical extract ofcannabinoids” or “cannabinoid botanical extract.” The concentrate can beobtained, e.g., by the extraction (e.g., hot solvent extraction,supercritical fluid extraction, etc.) of the plant tissue (e.g.,cannabis leaf or kava root root). The botanical extract will include thedesired components of the cannabis plant, e.g., kavalactones,tetrahydrocannabinols (THCs), cannabidiol (CBD), and/or cannabinoids.The extract can subsequently be purified employing, e.g., at least oneof filtration (e.g., charcoal filter), chromatography (e.g., HPLC),distillation, etc. The purification can be carried out to remove atleast a portion of the undesirable components of the plant, e.g., plantwaxes, plant lipids, and/or plant pigments such as chlorophylls, presentin the extract.

The active ingredient can be present in any suitable and appropriateamount, depending upon the desired dosing. For example, in a 100 mg thinfilm, the active ingredient can be present in an amount of about 0.01-60mg, about 0.1-50 mg, or about 0.5-40 mg.

“Flavoring agent” refers to a substance capable of providing a flavor.In addition to providing a palatable and pleasurable factor to the user,the flavoring agent can also mask undesirable flavors present in theOTF. In specific embodiments, the flavoring agent includes mintflavoring.

“Flavor extract” refers to a flavoring agent obtained by extracting apart of a raw material, often by using a solvent such as ethanol orwater. The majority of natural essences are obtained by extracting theessential oil from the blossoms, fruit, roots, etc., or the wholeplants, through four techniques: expression (when the oil is veryplentiful and easily obtained, as in lemon peel), absorption (generallyaccomplished by steeping in alcohol, as vanilla beans), maceration (usedto create smaller bits of the whole, as in making peppermint extract,etc.), and distillation (used with maceration, but in many cases, itrequires expert chemical knowledge and the erection of costly stills).

“Sweetener” refers to a substance capable of providing a palatable andpleasurable factor to the user, and/or capable of masking undesirableflavors present in the OTF. In specific embodiments, the sweetenerincludes at least one of sucralose and acesulfame potassium.

“Bitter blocker” refers to a substance capable of blocking ordiminishing the bitter taste of another substance.

“Palatable” refers to a substance (e.g., oral thin film) beingrelatively acceptable or agreeable to the palate or taste (e.g., sweetor savory), and in some cases to the olfactory nerves.

“Dye or pigment” refers to a substance that imparts coloring and/oraesthetic appearance to the OTF. A dye is a colored substance that hasan affinity to the substrate to which it is being applied. The dye isgenerally applied in an aqueous solution, and requires a mordant toimprove the fastness of the dye on the fiber. A pigment is a materialthat changes the color of reflected or transmitted light as the resultof wavelength-selective absorption. This physical process differs fromfluorescence, phosphorescence, and other forms of luminescence, in whicha material emits light. Both dyes and pigments appear to be coloredbecause they absorb some wavelengths of light more than others. Incontrast with a dye, a pigment generally is insoluble, and has noaffinity for the substrate. Some dyes can be precipitated with an inertsalt to produce a lake pigment, and based on the salt used they could bealuminum lake, calcium lake or barium lake pigments. In specificembodiments, the dye or pigment includes at least one of FD&C red, FD&Cblue, and FD&C yellow.

“Preservative” refers to an agent that extends the storage life of foodand non-food products by retarding or preventing deterioration offlavor, odor, color, texture, appearance, nutritive value, or safety. Apreservative need not provide a lethal, irreversible action resulting inpartial or complete microbial cell destruction or incapacitation.Sterilants, sanitizers, disinfectants, sporicides, viracides andtuberculocidal agents provide such an irreversible mode of action,sometimes referred to as “bactericidal” action. In contrast, apreservative can provide an inhibitory or bacteriostatic action that isreversible, in that the target microbes can resume multiplication if thepreservative is removed. The principal differences between apreservative and a sanitizer primarily involve mode of action (apreservative prevents growth rather than killing microorganisms) andexposure time (a preservative has days to months to act whereas asanitizer has at most a few minutes to act). In specific embodiments,the preservative includes at least one of sodium benzoate, methylparaben, propyl paraben, and sodium sorbate.

“Powder coating” refers to a substance that when used on the externalsurface of an OTF, prevents, minimizes and/or mitigates the likelihoodthat the OTF will stick to another adjoining OTF once packaged and/ormanufacturing equipment. As such, the powder coating can serve as aprocessing aid. The powder coating can also provide a vehicle foradditional flavoring. The size of the substances present in the powdercoating can vary as desired, but will typically be in the range of about1 μm to about 100 μm. In specific embodiments, the powder coating ispresent on at least one external surface, and includes at least one oftalc, microcrystalline cellulose, mint flavoring, sucralose, acesulfamepotassium, and tapioca starch.

“Tensile strength” refers to the maximum stress that a material canwithstand while being stretched or pulled before failing or breaking.Tensile strength is the opposite of compressive strength and the valuescan be quite different. Tensile strength is defined as a stress, whichis measured as force per unit area. For some non-homogeneous materials(or for assembled components) it can be reported just as a force or as aforce per unit width. In the SI system, the unit is the pascal (Pa) (ora multiple thereof, often megapascals (MPa), using the mega- prefix);or, equivalently to pascals, newtons per square meter (N/m²). Thecustomary unit is pounds-force per square inch (lbf/in² or psi), orkilo-pounds per square inch (ksi, or sometimes kpsi), which is equal to1000 psi; kilo-pounds per square inch are commonly used for conveniencewhen measuring tensile strengths. Typically, the testing involves takinga small sample with a fixed cross-section area, and then pulling it witha controlled, gradually increasing force until the sample changes shapeor breaks.

“Pliable” refers to the ability of an article to readily bend, beflexible, or to be supple.

“Non-sticky” refers to an article (e.g., thin film) not having theproperty of readily adhering or sticking to another surface (e.g.,another article, manufacturing equipment, packaging material, the user,etc.).

“Soft” refers to an article being relatively smooth and agreeable to thetouch; not rough or coarse. Such an article will be capable of producingagreeable sensations, pleasant or comfortable, upon contact with ananimal such as a human.

“Chewable configuration” refers to an article being manufactured in sucha manner and with ingredients, that it possesses a configuration capableof being readily chewed by an animal, such as a human.

“Malleable configuration” refers to refers to an article beingmanufactured in such a manner and with ingredients, that it possesses aconfiguration capable of being readily shaped or changed in form (e.g.,folded, bent, rolled, twisted, flexed, etc.) without breaking.

“Ductile property” refers to the ability of an article (e.g., thin film)being readily shaped or changed in form (e.g., folded, bent, rolled,twisted, flexed, etc.) without breaking.

“Mixing” refers to the act of combining, uniting, and/or joiningmultiple substances, into one mass, collection, or assemblage (e.g.,slurry), generally with a thorough and continuous contacting of theconstituents.

“Blending” refers to the act of mixing that employs equipment typicallyreferred to as a blender, or any device capable of blending a mixture.The mixing can provide a relatively smooth mixture, where theconstituents are inseparable. When used in the context of “high shearblending”, the blender has sharp edged blades and is used at high speed(1000-10,000 rpm).

“Mixture” refers to the mass, collection, or assemblage (e.g., slurry)obtained from the act of mixing.

“Cooling” refers to the act of removing or transferring a sufficientamount of energy (e.g., thermal energy), within a suitable period oftime, such that a decrease in temperature is experienced.

“Shearing” refers to the act of blending using sharp edgedblending/mixing blades.

“Slurry” refers to a relatively viscous mixture, but it flows freely.Upon condensing, the slurry will form a film.

As used herein, “contacting” refers to the act of touching, makingcontact, or of bringing substances into immediate proximity.

“Hot extruding” refers to the act of extruding an article, while thearticle is currently being heated, or was previously heated, such thatthe article is at an elevated temperature during the extruding process.The extruding process typically includes forcing the article through adie, thereby obtaining a desired cross-section.

“Casting” or “film casting” refers to the act of removing liquid (e.g.,water and/or solvent) from a mixture (e.g., slurry), such that a film isproduced.

“Condensing” refers to the act of removing liquid (e.g., water and/orsolvent).

“Heating” refers to the act of applying or transferring a sufficientamount of energy (e.g., thermal energy), within a suitable period oftime, such that a rise in temperature is experienced.

“Conductive heat transfer” or “conduction” refers to the transfer ofheat from one condensed material into another condensed material thatdoes not involve bulk motion within either of the condensed media.

“Radiative heat transfer” or “radiation” refers to the transfer of heatfrom one article to another by way of electromagnetic means, usually byinfrared radiation, but can also be microwave radiation.

“Convective heat transfer” or “convection” refers to the transfer ofheat from one article to another, by the movement of fluids. Convectionis usually the dominant form of heat transfer in liquids and gases.Although often discussed as a distinct method of heat transfer,convective heat transfer involves the combined processes of conduction(heat diffusion) and advection (heat transfer by bulk fluid flow).

Convection can be “forced” by movement of a fluid by means other thanbuoyancy forces (for example, a water pump in an automobile engine). Insome cases, natural buoyancy forces alone are entirely responsible forfluid motion when the fluid is heated, and this process is called“natural convection.” An example is the draft in a chimney or around anyfire. In natural convection, an increase in temperature produces areduction in density, which causes fluid motion due to pressures andforces when fluids of different densities are affected by gravity (orany g-force). For example, when water is heated on a stove, hot waterfrom the bottom of the pan rises, displacing the colder denser liquidwhich falls. After heating has stopped, mixing and conduction from thisnatural convection eventually result in a nearly homogeneous density,and even temperature.

Two types of convective heat transfer can be distinguished: free ornatural convection (passive) and forced convection (active). Activeconvection occurs when a fluid is forced to flow over the surface by anexternal source such as fans, by stirring, and pumps, creating anartificially induced convection current. Passive convention occurs whenfluid motion is caused by buoyancy forces that result from the densityvariations due to variations of temperature in the fluid. In the absenceof an external source, when the fluid is in contact with a hot surface,its molecules separate and scatter, causing the fluid to be less dense.As a consequence, the fluid is displaced while the cooler fluid getsdenser and the fluid sinks. Thus, the hotter volume transfers heattowards the cooler volume of that fluid. Familiar examples are theupward flow of air due to a fire or hot object and the circulation ofwater in a pot that is heated from below.

“In vacuo” refers to under vacuum. The vacuum can be a partial vacuum ora complete vacuum. Typically, the vacuum will be a partial vacuum (e.g.,a reduced pressure) such as, e.g., a pressure of less than about 30 mmmercury (Hg). Specifically, the reduced pressure can be less than about29 mm mercury (Hg). More specifically, the reduced pressure can be about10 to about 29 mm of mercury (Hg).

“Packaging material” refers to those materials and substances employedto package the product (e.g., thin film). Such materials are widelyknown to those of skill in the art.

“Enclosing” refers to the packaging materials containing or holding theproduct (e.g., thin film) by surrounding the product with the packagingmaterial. The packaging materials can partially surround the product, orcan completely surround the product. Typically, to ensure safety (e.g.,no tampering with product) and freshness, the packaging materials willcompletely surround the product. For example, the packaging materialscan form a relatively vapor impermeable enclosure of the product.

“Printed indicia” refers to a marking, image, text, and/or symbollocated on the surface of the packaging material. The indicia can beplaced on the surface of the packaging material by any suitable means(e.g., ink printing, laser printing, etc.). The indicia can include,e.g., a printed message or instructions, list of ingredients (active andinactive), weight of product, manufacturer name and address,manufacturer trademark, etc.

Referring to FIG. 1, an example of a block flow diagram illustrating amethod of preparing an oral thin film (100) is shown, according to someembodiments. A combination of lipid, emulsifier, and solvent (102) ismixed to provide a uniform first mixture (106). Active ingredient isadded (108) to the uniform first mixture (106), to form a thickenedsecond mixture (110). Flavoring agent, sweetener, coloring agent,non-sticky binder, and sticky binder are added to the thickened secondmixture (110), to provide a slurry (114). The slurry (114) is cooled,sheared, mixed, cast, and condensed (116) to provide an oral thin film(120). Alternatively, the slurry (114) is hot extruded, cast, andcondensed (118) to provide an oral thin film (120).

The combination of lipid, emulsifier, and solvent (102) is mixed (104)to provide a uniform first mixture (106). The mixing (104) willtypically be carried out at an elevated temperature (e.g., about130-140° F. or 54.4-60° C.), sufficient to provide the uniform firstmixture (106). Additionally, mixing (104) will typically be carried outfor a suitable period of time (e.g., about 3 minutes), sufficient toprovide the uniform first mixture (106). The mixing (104) can be carriedout in any suitable manner, employing suitable equipment known to thoseof skill in the art, sufficient to provide the uniform first mixture(106). For example, the mixing (104) can include blending, which can becarried out employing a blender.

The uniform first mixture (106) and active ingredient can be contacted(108), to provide a thickened second mixture (110). Typically, theactive ingredient can be added (108) to the uniform first mixture (106).The contacting (108) can include mixing. The mixing (108) will typicallybe carried out at room temperature (e.g., about 70° F.), and for asuitable period of time (e.g., up to about 5 minutes), sufficient toprovide the thickened second mixture (110). The mixing (108) can becarried out in any suitable manner, employing suitable equipment knownto those of skill in the art, sufficient to provide the thickened secondmixture (110). For example, the mixing (108) can include blending, whichcan be carried out employing a blender.

Flavoring agent, sweetener, coloring agent, non-sticky binder, andsticky binder are contacted with the thickened second mixture (110), toprovide a slurry (114). Typically, the flavoring agent, sweetener,coloring agent, non-sticky binder, and sticky binder can be added (112)to the thickened second mixture (110), to provide a slurry (114). Thecontacting can include mixing. The mixing will typically be carried outat room temperature (e.g., about 70° F.), and for a suitable period oftime (e.g., up to about 5 minutes), sufficient to provide the slurry(114). The mixing can be carried out in any suitable manner, employingsuitable equipment known to those of skill in the art, sufficient toprovide the slurry (114). For example, the mixing can include blending,which can be carried out employing a blender.

The slurry (114) is hot extruded, cast, and condensed (118), to providethe thin film (120). With some active ingredients (e.g., caffeine), uponcooling, the active ingredient will fall out of solution (i.e.,precipitate), due to poor solubility issues. With such activeingredients, the slurry (114) can be cooled, sheared, mixed, cast, andcondensed (116) to provide the thin film (120).

The slurry (114) will typically have up to about 85 wt. % water. Assuch, the condensing can be carried out until the thin film (120) hasthe requisite amount of water (e.g., about 4-18 wt. %). Typically, thecondensing will be carried out at an elevated temperature (e.g., atleast about 70° C. (158° F.)). Additionally, the condensing willtypically be carried out for an extended period of time (e.g., at leastabout 10 minutes). The condensing can be carried out in any suitablemanner, employing suitable equipment known to those of skill in the art,sufficient to provide the thin film (120). For example, the condensingcan be carried out employing an oven that utilizes passive convection.Alternatively, the condensing can be carried out employing an oven thatutilizes active convection. In addition to (or in replace of) theelevated temperature, the condensing can be carried out at a reducedpressure (e.g., in vacuo).

Specific ranges, values, and embodiments provided below are forillustration purposes only and do not otherwise limit the scope of theinvention, as defined by the claims. The specific ranges, values, andembodiments described below encompass all combinations andsub-combinations of each disclosed range, value, and embodiment, whetheror not expressly described as such.

SPECIFIC RANGES, VALUES, AND EMBODIMENTS

In specific embodiments, the thin film is an oral thin film (OTF).

In specific embodiments, the thin film is an oral dissolvable film(ODF).

In specific embodiments, the thin film is an oral thin film, which isedible and pharmaceutically safe and effective.

In specific embodiments, the thin film is configured for application tomucosal tissue or a mucosal surface.

In specific embodiments, the thin film is configured for application toat least one of the mouth, buccal cavity, nose, eye, vagina, and rectum.

In specific embodiments, the thin film is configured for application tothe mouth.

In specific embodiments, the thin film is configured for application tothe buccal cavity.

In specific embodiments, the thin film is configured for application tothe nose.

In specific embodiments, the thin film is configured for application tothe eye.

In specific embodiments, the thin film is configured for application tothe vagina.

In specific embodiments, the thin film is configured for application tothe rectum.

In specific embodiments, the thin film is configured for delivering theactive ingredient to at least one of the mouth, buccal cavity, nose,eye, vagina, and rectum.

In specific embodiments, the thin film is configured for delivering theactive ingredient to the mouth.

In specific embodiments, the thin film is configured for delivering theactive ingredient to the buccal cavity.

In specific embodiments, the thin film is configured for delivering theactive ingredient to the nose.

In specific embodiments, the thin film is configured for delivering theactive ingredient to the eye.

In specific embodiments, the thin film is configured for delivering theactive ingredient to the vagina.

In specific embodiments, the thin film is configured for delivering theactive ingredient to the rectum.

In specific embodiments, the solvent includes at least one of water andethanol.

In specific embodiments, the solvent includes water and ethanol.

In specific embodiments, the solvent includes water.

In specific embodiments, the solvent includes ethanol.

In specific embodiments, the solvent is present in at least about 2 wt.%.

In specific embodiments, the solvent is present in up to about 24 wt. %.

In specific embodiments, the solvent is present in about 2-24 wt. %.

In specific embodiments, the solvent is present in at least about 4 wt.%.

In specific embodiments, the solvent is present in up to 12 wt. %.

In specific embodiments, the solvent is present in about 4-12 wt. %.

In specific embodiments, the solvent is present in about 8 wt. %.

In specific embodiments, the binder includes at least one of pectin,microcrystalline cellulose, xanthan gum, locust bean gum, guar gum, gumarabic, gum tragacanth, gum karaya, beta glucan, glucomannan, tapiocastarch, carrageenan, xanthan gum, gellan gum, alginic acid or sodiumalginate, konjac gum, tara gum, chitosan, agar, maltodextrin, polyvinylalcohol, pullulan, polycarbophil, povidone, hydroxypropylmethylcellulose, hydroxypropyl cellulose, hydroxypropyl starch, andpolyethylene glycol.

In specific embodiments, the binder is acidic.

In specific embodiments, the binder includes at least one of pectin andmicrocrystalline cellulose.

In specific embodiments, the binder includes pectin.

In specific embodiments, the binder includes microcrystalline cellulose.

In specific embodiments, the binder is sticky.

In specific embodiments, the binder is non-sticky.

In specific embodiments, the binder is present in at least about 4 wt.%.

In specific embodiments, the binder is present in up to about 50 wt. %.

In specific embodiments, the binder is present in about 4-50 wt. %.

In specific embodiments, the binder is present in at least about 10 wt.%.

In specific embodiments, the binder is present in up to about 36 wt. %

In specific embodiments, the binder is present in about 10-36 wt. %.

In specific embodiments, the binder is present in about 25 wt. %.

In specific embodiments, the lipid is absent.

In specific embodiments, the lipid is present.

In specific embodiments, the lipid includes at least one of almond oil,argan oil, avocado oil, canola oil, cashew oil, castor oil, cocoa butter(e.g., deodorized cocoa butter oil), coconut oil, colza oil, corn oil,cottonseed oil, grape seed oil, hazelnut oil, hemp oil, hydroxylatedlecithin, lecithin, linseed oil, macadamia oil, mango butter, marulaoil, mongongo nut oil, olive oil, palm kernel oil, palm oil, peanut oil,pecan oil, perilla oil, pine nut oil, pistachio oil, poppy seed oil,pumpkin seed oil, rice bran oil, safflower oil, sesame oil, shea butter,soybean oil, sunflower oil, walnut oil, grape seed oil, and watermelonseed oil.

In specific embodiments, the lipid includes at least one of hydroxylatedlecithin and deodorized cocoa butter oil.

In specific embodiments, the lipid includes hydroxylated lecithin.

In specific embodiments, the lipid includes deodorized cocoa butter oil.

In specific embodiments, the lipid is present in at least about 4 wt. %.

In specific embodiments, the lipid is present in up to about 22 wt. %.

In specific embodiments, the lipid is present in about 0-22 wt. %.

In specific embodiments, the lipid is present in about 4-22 wt. %.

In specific embodiments, the lipid is present in at least about 10 wt.%.

In specific embodiments, the lipid is present in up to about 18 wt. %.

In specific embodiments, the lipid is present in about 10-18 wt. %.

In specific embodiments, the lipid is present in about 14.8 wt. %.

In specific embodiments, the emulsifier includes at least one ofglycerin, ethoxylated monoglycerides, and ethoxylated diglycerides.

In specific embodiments, the emulsifier includes at least one ofglycerin, propylene glycol, and polyethylene glycol.

In specific embodiments, the emulsifier includes glycerin.

In specific embodiments, the emulsifier is present in at least about 3wt. %.

In specific embodiments, the emulsifier is present in up to about 22 wt.%.

In specific embodiments, the emulsifier is present in about 3-22 wt. %.

In specific embodiments, the emulsifier is present in at least about 8wt. %.

In specific embodiments, the emulsifier is present in up to about 18 wt.%.

In specific embodiments, the emulsifier is present in about 8-18 wt. %.

In specific embodiments, the emulsifier is present in about 14 wt. %.

In specific embodiments, the thin film further includes an absorptionenhancer.

In specific embodiments, the thin film further includes a flavoringagent.

In specific embodiments, the flavoring agent includes at least one of aliquid flavor extract and a solid flavor extract.

In specific embodiments, the flavoring agent includes a liquid flavorextract.

In specific embodiments, the flavoring agent includes a solid flavorextract.

In specific embodiments, the thin film further includes a sweetener.

In specific embodiments, the sweetener includes at least one ofsucralose, acesulfame potassium, ammonium glycyrrhizinate, naringindihydrochalcone, neohesperidin dihydrochalcone, neotame, erythritol,xylitol, sucrose, sodium saccharine, stevia, alitame, fructose,sucralose, and aspartame.

In specific embodiments, the sweetener includes at least one ofsucralose, acesulfame potassium, and ammonium glycyrrhizinate.

In specific embodiments, the sweetener includes at least one ofsucralose and acesulfame potassium.

In specific embodiments, the sweetener is present in at least about 1wt. %.

In specific embodiments, the sweetener is present in up to about 40 wt.%.

In specific embodiments, the sweetener is present in about 1-40 wt. %.

In specific embodiments, the sweetener is present in at least about 6wt. %.

In specific embodiments, the sweetener is present in up to about 14 wt.%.

In specific embodiments, the sweetener is present in about 6-14 wt. %.

In specific embodiments, the sweetener is present in about 10 wt. %.

In specific embodiments, the thin film further includes a dye orpigment.

In specific embodiments, the dye or pigment includes at least one ofFD&C food colorings and vegetable derived food colorings.

In specific embodiments, the dye or pigment includes FD&C food colorings(e.g., FD&C red, FD&C blue, and/or FD&C yellow).

In specific embodiments, the dye or pigment includes vegetable derivedfood colorings.

In specific embodiments, the dye or pigment is present in up to about0.1 wt. %.

In specific embodiments, the dye or pigment is present in about 0-0.1wt. %.

In specific embodiments, the dye or pigment is present in at least about0.01 wt. %.

In specific embodiments, the dye or pigment is present in up to about0.04 wt. %.

In specific embodiments, the dye or pigment is present in about0.01-0.04 wt. %.

In specific embodiments, the dye or pigment is present in about 0.2 wt.%.

In specific embodiments, the thin film further includes a preservative.

In specific embodiments, the preservative includes at least one ofbenzoate salt, sorbate salt, and natamycin.

In specific embodiments, the preservative includes sodium benzoate.

In specific embodiments, the preservative includes at least one ofsodium benzoate, methyl paraben, propyl paraben, and sodium sorbate.

In specific embodiments, the preservative is present in up to about 0.1wt. %.

In specific embodiments, the preservative is present in about 0-0.1 wt.%.

In specific embodiments, the preservative is present in up to about 0.02wt. %.

In specific embodiments, the preservative is present in about 0-0.02 wt.%.

In specific embodiments, the dough conditioner includes at least one ofglycerin, ethoxylated monoglycerides, and ethoxylated diglycerides.

In specific embodiments, the dough conditioner includes glycerin.

In specific embodiments, the dough conditioner includes ethoxylatedmonoglycerides.

In specific embodiments, the dough conditioner includes ethoxylateddiglycerides.

In specific embodiments, the dough conditioner is present in about 0-25wt. %.

In specific embodiments, the dough conditioner is present in about 1-25wt. %.

In specific embodiments, the dough conditioner is present in about 1-15wt. %.

In specific embodiments, the thin film further includes a powdercoating.

In specific embodiments, the powder coating includes at least one oftalc, microcrystalline cellulose, powdered flavoring agent, powderedsweetener, and powdered tapioca starch.

In specific embodiments, the powder coating includes at least one oftalc and microcrystalline cellulose.

In specific embodiments, the powder coating includes talc andmicrocrystalline cellulose.

In specific embodiments, the powder coating is present in up to about 20wt. %.

In specific embodiments, the powder coating is present in about 0-20 wt.%.

In specific embodiments, the powder coating is present in at least about5 wt. %.

In specific embodiments, the powder coating is present in up to about 15wt. %.

In specific embodiments, the powder coating is present in about 5-15 wt.%.

In specific embodiments, the powder coating is present in about 10 wt.%.

In specific embodiments, the botanical extract includes less than about5 wt. % plant waxes.

In specific embodiments, the botanical extract includes less than about1 wt. % plant waxes.

In specific embodiments, the botanical extract includes less than about0.5 wt. % plant waxes.

In specific embodiments, the botanical extract includes less than about5 wt. % plant lipids.

In specific embodiments, the botanical extract includes less than about1 wt. % plant lipids.

In specific embodiments, the botanical extract includes less than about0.5 wt. % plant lipids.

In specific embodiments, the botanical extract includes less than about5 wt. % plant pigments.

In specific embodiments, the botanical extract includes less than about1 wt. % plant pigments.

In specific embodiments, the botanical extract includes less than about0.5 wt. % plant pigments.

In specific embodiments, the botanical extract includes less than about5 wt. % chlorophylls.

In specific embodiments, the botanical extract includes less than about1 wt. % chlorophylls.

In specific embodiments, the botanical extract includes less than about0.5 wt. % chlorophylls.

In specific embodiments, the botanical extract includes at least about50 wt. %, in the aggregate, of kavalactones, tetrahydrocannabinols(THCs), cannabidiol (CBD), and cannabinoids.

In specific embodiments, the botanical extract includes at least about70 wt. %, in the aggregate, of kavalactones, tetrahydrocannabinols(THCs), cannabidiol (CBD), and cannabinoids.

In specific embodiments, the botanical extract includes at least about75 wt. %, in the aggregate, of kavalactones, tetrahydrocannabinols(THCs), cannabidiol (CBD), and cannabinoids.

In specific embodiments, the botanical extract includes at least about80 wt. %, in the aggregate, of kavalactones, tetrahydrocannabinols(THCs), cannabidiol (CBD), and cannabinoids.

In specific embodiments, the active ingredient is present in at leastabout 20 wt. %.

In specific embodiments, the active ingredient is present in at leastabout 25 wt. %.

In specific embodiments, the active ingredient is present in at leastabout 30 wt. %.

In specific embodiments, the active ingredient is present in at leastabout 35 wt. %.

In specific embodiments, the active ingredient is present in at leastabout 40 wt. %.

In specific embodiments, the active ingredient is present in up to about50 wt. %.

In specific embodiments, the active ingredient is present in up to about45 wt. %.

In specific embodiments, the active ingredient is present in up to about40 wt. %.

In specific embodiments, the active ingredient is present in up to about35 wt. %.

In specific embodiments, the active ingredient is present in about 25-45wt. %.

In specific embodiments, the active ingredient is present in about 25-40wt. %.

In specific embodiments, the active ingredient is at least partiallyencapsulated by the lipid.

In specific embodiments, at least about 10 wt. % of the activeingredient is encapsulated by the lipid.

In specific embodiments, at least about 25 wt. % of the activeingredient is encapsulated by the lipid.

In specific embodiments, at least about 35 wt. % of the activeingredient is encapsulated by the lipid.

In specific embodiments, at least about 50 wt. % of the activeingredient is encapsulated by the lipid.

In specific embodiments, at least about 60 wt. % of the activeingredient is encapsulated by the lipid.

In specific embodiments, at least about 75 wt. % of the activeingredient is encapsulated by the lipid.

In specific embodiments, at least about 85 wt. % of the activeingredient is encapsulated by the lipid.

In specific embodiments, at least about 90 wt. % of the activeingredient is encapsulated by the lipid.

In specific embodiments, at least about 95 wt. % of the activeingredient is encapsulated by the lipid.

In specific embodiments, up to about 99 wt. % of the active ingredientis encapsulated by the lipid.

In specific embodiments, up to about 90 wt. % of the active ingredientis encapsulated by the lipid.

In specific embodiments, up to about 75 wt. % of the active ingredientis encapsulated by the lipid.

In specific embodiments, up to about 50 wt. % of the active ingredientis encapsulated by the lipid.

In specific embodiments, the active ingredient is completelyencapsulated by the lipid.

In specific embodiments, the lipid encapsulates the active ingredient bythe formation of liposomes and/or micelles.

In specific embodiments, the lipid encapsulates the active ingredient bythe formation of liposomes.

In specific embodiments, the lipid encapsulates the active ingredient bythe formation of unilamellar liposomes.

In specific embodiments, the lipid encapsulates the active ingredient bythe formation of multilamellar liposomes.

In specific embodiments, the lipid encapsulates the active ingredient bythe formation of micelles.

In specific embodiments, the film is configured and formulated for theimmediate release (IR) of at least one of kavalactones,tetrahydrocannabinols (THCs), cannabidiol (CBD), and cannabinoids.

In specific embodiments, the film is configured and formulated for thesustained release (SR), delayed release (DR), modified release (MR),extended release (XR), or controlled release (CR) of at least one ofkavalactones, tetrahydrocannabinols (THCs), cannabidiol (CBD), andcannabinoids.

In specific embodiments, the film is configured and formulated for thesustained release (SR) of at least one of kavalactones,tetrahydrocannabinols (THCs), cannabidiol (CBD), and cannabinoids.

In specific embodiments, the film is configured and formulated for thedelayed release (DR) of at least one of kavalactones,tetrahydrocannabinols (THCs), cannabidiol (CBD), and cannabinoids.

In specific embodiments, the film is configured and formulated for themodified release (MR) of at least one of kavalactones,tetrahydrocannabinols (THCs), cannabidiol (CBD), and cannabinoids.

In specific embodiments, the film is configured and formulated for theextended release (XR) of at least one of kavalactones,tetrahydrocannabinols (THCs), cannabidiol (CBD), and cannabinoids.

In specific embodiments, the film is configured and formulated for thecontrolled release (CR) of at least one of kavalactones,tetrahydrocannabinols (THCs), cannabidiol (CBD), and cannabinoids.

In specific embodiments, the botanical extract includes at least about50 wt. %, in the aggregate, of kavalactones, tetrahydrocannabinols(THCs), cannabidiol (CBD), and cannabinoids.

In specific embodiments, the botanical extract is enriched with at leastone of kavalactones, tetrahydrocannabinols (THCs), cannabidiol (CBD),and cannabinoids.

In specific embodiments, the botanical extract is enriched withtetrahydrocannabinols (THCs).

In specific embodiments, the botanical extract is enriched withcannabidiol (CBD).

In specific embodiments, the botanical extract is enriched withcannabinoids.

In specific embodiments, the thin film is palatable to a human.

In specific embodiments, the external surfaces of the thin film have asmooth texture.

In specific embodiments, the thin film has a high tensile strength.

In specific embodiments, the thin film is pliable.

In specific embodiments, the thin film is non-sticky to touch.

In specific embodiments, the thin film does not readily stick to anotherthin film.

In specific embodiments, the thin film is relatively soft to touch.

In specific embodiments, the thin film has a chewable configuration.

In specific embodiments, the thin film has a resilient configuration.

In specific embodiments, the thin film has an elastic or malleableconfiguration.

In specific embodiments, the thin film has a ductile property.

In specific embodiments, the thin film further includes a bitterblocker.

In specific embodiments, the thin film further includes a powder coatingpresent on at least one external surface of the thin film.

In specific embodiments, the thin film further includes a powder coatingpresent on two opposing external surfaces of the thin film.

In specific embodiments, the method of preparing a thin film is carriedout in the order indicated.

In specific embodiments, each of the steps of the method of preparing athin film is carried out in the order indicated.

In specific embodiments, the mixing includes blending.

In specific embodiments, the mixing is carried out at a temperature ofabout 130-140° F. (54.4-60° C.).

In specific embodiments, the contacting of the active ingredient withthe uniform first mixture further includes contacting at least one of asweetener, flavoring agent, and dye or pigment with the uniform firstmixture.

In specific embodiments, the contacting of the binder with the thickenedsecond mixture includes initially contacting a non-sticky binder withthe thickened second mixture, and subsequently contacting a stickybinder with the thickened second mixture.

In specific embodiments, the contacting of the binder with the thickenedsecond mixture includes initially contacting microcrystalline cellulosewith the thickened second mixture, and subsequently contacting pectinwith the thickened second mixture.

In specific embodiments, the condensing includes heating at atemperature of at least about 75° F. (23.9° C.).

In specific embodiments, the condensing includes heating at atemperature of at least about 100° F. (37.8° C.).

In specific embodiments, the condensing includes heating at atemperature of at least about 125° F. (51.7° C.).

In specific embodiments, the condensing includes heating at atemperature of at least about 150° F. (65.6° C.).

In specific embodiments, the condensing includes heating at atemperature of up to about 200° F. (93.4° C.).

In specific embodiments, the condensing includes heating at atemperature of up to about 150° F. (65.6° C.).

In specific embodiments, the condensing includes heating at atemperature of about 75° F. (23.9° C.) to about 200° F. (93.4° C.).

In specific embodiments, the condensing includes heating at atemperature of about 75° F. (23.9° C.) to about 175° F. (79.4° C.).

In specific embodiments, the condensing includes heating at atemperature of about 75° F. (23.9° C.) to about 150° F. (65.6° C.).

In specific embodiments, the condensing is carried out for at leastabout 10 minutes.

In specific embodiments, the condensing is carried out for at leastabout 30 minutes.

In specific embodiments, the condensing is carried out for at leastabout 1 hour.

In specific embodiments, the condensing is carried out for at leastabout 2 hours.

In specific embodiments, the condensing is carried out for at leastabout 6 hours.

In specific embodiments, the condensing is carried out for at leastabout 8 hours.

In specific embodiments, the condensing is carried out for at leastabout 12 hours.

In specific embodiments, the condensing is carried out for at leastabout 18 hours.

In specific embodiments, the condensing is carried out for at leastabout 24 hours.

In specific embodiments, the condensing is carried out for at leastabout 48 hours.

In specific embodiments, the condensing includes heating with passiveconvection.

In specific embodiments, the condensing includes heating with activeconvection.

In specific embodiments, the condensing is carried out in vacuo.

In specific embodiments, the method of preparing a thin film furtherincludes contacting a powder coating with at least one external surfaceof the thin film.

In specific embodiments, the method of preparing a thin film furtherincludes contacting a powder coating with two opposing external sides ofthe thin film.

In specific embodiments, the system includes at least about 2 thinfilms.

In specific embodiments, the system includes at least about 5 thinfilms.

In specific embodiments, the system includes at least about 10 thinfilms.

In specific embodiments, the system includes at least about 25 thinfilms.

In specific embodiments, each of the multiple thin films of the systemindependently has a dimension of at least 15 mm×25 mm.

In specific embodiments, each of the multiple thin films of the systemindependently has a dimension of up to 35 mm×50 mm.

In specific embodiments, each of the multiple thin films of the systemindependently has a dimension of 23 mm×38 mm, ±5 mm.

In specific embodiments, each of the multiple thin films of the systemindependently has a dimension of 23 mm×38 mm, ±3 mm.

In specific embodiments, each of the multiple thin films of the systemindependently has a thickness of about 0.01 mm to about 20 mm.

In specific embodiments, each of the multiple thin films of the systemindependently has a thickness of at least about 0.01 mm.

In specific embodiments, each of the multiple thin films of the systemindependently has a thickness of up to about 20 mm.

In specific embodiments, each of the multiple thin films of the systemindependently has a thickness of about 0.03 mm to about 1 mm.

In specific embodiments, each of the multiple thin films of the systemindependently weighs about 10 mg to about 80 mg.

In specific embodiments, each of the multiple thin films of the systemindependently weighs at least about 10 mg.

In specific embodiments, each of the multiple thin films of the systemindependently weighs about up to about 80 mg.

In specific embodiments, each of the multiple thin films of the systemindependently weighs about 20 mg to about 70 mg.

In specific embodiments, each of the multiple thin films of the systemindependently weighs at least about 30 mg.

In specific embodiments, each of the multiple thin films of the systemindependently weighs up to at least about 400 mg.

In specific embodiments, each of the multiple thin films of the systemindependently weighs about 30 mg to about 400 mg.

In specific embodiments, each of the multiple thin films of the systemindependently weighs about 60 mg to about 300 mg.

Enumerated Embodiments

Specific enumerated embodiments [1] to [107] provided below are forillustration purposes only, and do not otherwise limit the scope of thedisclosed subject matter, as defined by the claims. These enumeratedembodiments encompass all combinations, sub-combinations, and multiplyreferenced (e.g., multiply dependent) combinations described therein.

[1.] An oral dissolvable film that includes:

(a) solvent,

(b) binder,

(c) optionally a lipid,

(d) emulsifier,

(e) botanical extract,

(f) optionally a dough conditioner,

(g) optionally a flavoring agent,

(h) optionally a sweetener,

(i) optionally a dye or pigment,

(j) a powder coating on at least one external surface, and

(k) optionally a preservative.

[2.] The oral dissolvable film of claim 1, wherein the botanical extractincludes less than about 1 wt. % plant waxes.[3.] The oral dissolvable film of claim 1, wherein the botanical extractincludes less than about 1 wt. % plant lipids.[4.] The oral dissolvable film of claim 1, wherein the botanical extractincludes less than about 1 wt. % plant pigments.[5.] The oral dissolvable film of claim 1, wherein the botanical extractincludes less than about 1 wt. % chlorophylls.[6.] The oral dissolvable film of claim 1, wherein the botanical extractincludes at least about 70 wt. % in the aggregate of kavalactones,tetrahydrocannabinols (THCs), cannabidiol (CBD), and cannabinoids.[7.] The oral dissolvable film of claim 1, wherein at least about 50 wt.% of the botanical extract is encapsulated by the lipid.[8.] The oral dissolvable film of claim 1, wherein the botanical extractis present in at least about 20 wt. % of the thin film.[9.] The oral dissolvable film of claim 1, configured and formulated forthe immediate release (IR) of at least one of kavalactones,tetrahydrocannabinols (THCs), cannabidiol (CBD), and cannabinoids.[10]. The oral dissolvable film of claim 1, configured and formulatedfor the sustained release (SR), delayed release (DR), modified release(MR), extended release (XR), or controlled release (CR) of at least oneof kavalactones, tetrahydrocannabinols (THCs), cannabidiol (CBD), andcannabinoids.[11]. The oral dissolvable film of claim 1, wherein the doughconditioner includes at least one of glycerin, ethoxylatedmonoglycerides, and ethoxylated diglycerides.[12.] The thin film of the above embodiment, wherein the solventincludes at least one of water and ethanol.[13.] The thin film of any one of the above embodiments, wherein thesolvent is present in about 2-24 wt. %.[14.] The thin film of any one of the above embodiments, wherein thesolvent is present in about 4-12 wt. %.[15.] The thin film of any one of the above embodiments, wherein thesolvent is present in about 8 wt. %.[16.] The thin film of any one of the above embodiments, wherein thebinder includes at least one of pectin, microcrystalline cellulose,xanthan gum, locust bean gum, guar gum, gum arabic, gum tragacanth, gumkaraya, beta glucan, glucomannan, tapioca starch, carrageenan, xanthangum, gellan gum, alginic acid or sodium alginate, konjac gum, tara gum,chitosan, agar, maltodextrin, polyvinyl alcohol, pullulan,polycarbophil, povidone, hydroxypropyl methylcellulose, hydroxypropylcellulose, hydroxypropyl starch, and polyethylene glycol.[17.] The thin film of any one of the above embodiments, wherein thebinder is acidic.[18.] The thin film of any one of the above embodiments, wherein thebinder is present in about 4-50 wt. %.[19.] The thin film of any one of the above embodiments, wherein thebinder is present in about 10-36 wt. %.[20.] The thin film of any one of the above embodiments, wherein thebinder is present in about 25 wt. %.[21.] The thin film of any one of the above embodiments, wherein thelipid is absent.[22.] The thin film of any one of the above embodiments, wherein thelipid is present.[23.] The thin film of any one of the above embodiments, wherein thelipid includes at least one of almond oil, argan oil, avocado oil,canola oil, cashew oil, castor oil, cocoa butter (e.g., deodorized cocoabutter oil), coconut oil, colza oil, corn oil, cottonseed oil, grapeseed oil, hazelnut oil, hemp oil, hydroxylated lecithin, lecithin,linseed oil, macadamia oil, mango butter, marula oil, mongongo nut oil,olive oil, palm kernel oil palm oil, peanut oil, pecan oil, perilla oil,pine nut oil, pistachio oil, poppy seed oil, pumpkin seed oil, rice branoil, safflower oil, sesame oil, Shea butter, soybean oil, sunflower oil,walnut oil, grape seed oil, and watermelon seed oil.[24.] The thin film of any one of the above embodiments, wherein thelipid is present in about 0-22 wt. %.[25.] The thin film of any one of the above embodiments, wherein thelipid is present in about 4-22 wt. %.[26.] The thin film of any one of the above embodiments, wherein thelipid is present in about 10-18 wt. %.[27.] The thin film of any one of the above embodiments, wherein thelipid is present in about 14.8 wt. %.[28.] The thin film of any one of the above embodiments, wherein theemulsifier includes at least one of glycerin, propylene glycol, andpolyethylene glycol.[29.] The thin film of any one of the above embodiments, wherein theemulsifier is present in about 3-22 wt. %.[30.] The thin film of any one of the above embodiments, wherein theemulsifier is present in about 8-18 wt. %.[31.] The thin film of any one of the above embodiments, wherein theemulsifier is present in about 14 wt. %.[32.] The thin film of any one of the above embodiments, furtherincluding a flavoring agent.[33.] The thin film of any one of the above embodiments, furtherincluding a flavoring agent, including at least one of a liquid flavorextract and a solid flavor extract.[34.] The thin film of any one of the above embodiments, furtherincluding a sweetener.[35.] The thin film of any one of the above embodiments, furtherincluding a sweetener selected from at least one of sucralose,acesulfame potassium, ammonium glycyrrhizinate, naringindihydrochalcone, neohesperidin dihydrochalcone, neotame, erythritol,xylitol, sucrose, sodium saccharine, stevia, alitame, fructose, andaspartame.[36.] The thin film of any one of the above embodiments, furtherincluding a sweetener, present in about 1-40 wt. %.[37.] The thin film of any one of the above embodiments, furtherincluding a sweetener, present in about 6-14 wt. %.[38.] The thin film of any one of the above embodiments, furtherincluding a sweetener, present in about 10 wt. %.[39.] The thin film of any one of the above embodiments, furtherincluding a dye or pigment.[40.] The thin film of any one of the above embodiments, furtherincluding a dye or pigment selected from at least one of FD&C foodcolorings and vegetable derived food colorings.[41.] The thin film of any one of the above embodiments, furtherincluding a dye or pigment, present in about 0-0.1 wt. %.[42.] The thin film of any one of the above embodiments, furtherincluding a dye or pigment, present in about 0.01-0.04 wt. %.[43.] The thin film of any one of the above embodiments, furtherincluding a dye or pigment, present in about 0.2 wt. %.[44.] The thin film of any one of the above embodiments, furtherincluding a preservative.[45.] The thin film of any one of the above embodiments, furtherincluding a preservative selected from at least one of benzoate salt(e.g., sodium benzoate), sorbate salt (e.g., sodium sorbate), methylparaben, propyl paraben, and natamycin.[46.] The thin film of any one of the above embodiments, furtherincluding a preservative, present in about 0-0.1 wt. %.[47.] The thin film of any one of the above embodiments, furtherincluding a preservative, present in about 0-0.02 wt. %.[48.] The thin film of any one of the above embodiments, furtherincluding a dough conditioner.[49.] The thin film of any one of the above embodiments, furtherincluding a dough conditioner that includes at least one of glycerin,ethoxylated monoglycerides, and ethoxylated diglycerides.[50.] The thin film of any one of the above embodiments, furtherincluding a dough conditioner that includes glycerin.[51.] The thin film of any one of the above embodiments, furtherincluding a dough conditioner that includes ethoxylated monoglycerides.[52.] The thin film of any one of the above embodiments, furtherincluding a dough conditioner that includes ethoxylated diglycerides.[53.] The thin film of any one of the above embodiments, furtherincluding a dough conditioner present in about 0-25 wt. %.[54.] The thin film of any one of the above embodiments, furtherincluding a dough conditioner present in about 1-25 wt. %.[55.] The thin film of any one of the above embodiments, furtherincluding a dough conditioner present in about 1-15 wt. %.[56.] The thin film of any one of the above embodiments, furtherincluding a powder coating.[57.] The thin film of any one of the above embodiments, furtherincluding a powder coating selected from at least one of talc,microcrystalline cellulose, flavoring agent (e.g., mint flavoring),sweetener (e.g., sucralose and/or acesulfame potassium), and tapiocastarch.[58.] The thin film of any one of the above embodiments, furtherincluding a powder coating, present in about 0-20 wt. %.[59.] The thin film of any one of the above embodiments, furtherincluding a powder coating, present in about 5-15 wt. %.[60.] The thin film of any one of the above embodiments, furtherincluding a powder coating, present in about 10 wt. %.[61.] The thin film of any one of the above embodiments, wherein theactive ingredient is present in at least about 25 wt. %.[62.] The thin film of any one of the above embodiments, wherein theactive ingredient is present in at least about 30 wt. %.[63.] The thin film of any one of the above embodiments, wherein theactive ingredient is present in at least about 35 wt. %.[64.] The thin film of any one of the above embodiments, wherein theactive ingredient is present in at least about 40 wt. %.[65.] The thin film of any one of the above embodiments, wherein theactive ingredient is present in about 25-40 wt. %.[66.] The thin film of any one of the above embodiments, wherein theactive ingredient is at least partially encapsulated by the lipid.[67.] The thin film of any one of the above embodiments, wherein atleast about 25 wt. % of the active ingredient is encapsulated by thelipid.[68.] The thin film of any one of the above embodiments, wherein atleast about 50 wt. % of the active ingredient is encapsulated by thelipid.[69.] The thin film of any one of the above embodiments, wherein atleast about 75 wt. % of the active ingredient is encapsulated by thelipid.[70.] The thin film of any one of the above embodiments, the activeingredient is completely encapsulated by the lipid.[71.] The thin film of any one of the above embodiments, which ispalatable to a human.[72.] The thin film of any one of the above embodiments, wherein theexternal surfaces have a smooth texture.[73.] The thin film of any one of the above embodiments, which has ahigh tensile strength.[74.] The thin film of any one of the above embodiments, which ispliable.[75.] The thin film of any one of the above embodiments, which isnon-sticky to touch.[76.] The thin film of any one of the above embodiments, which does notreadily stick to another thin film.[77.] The thin film of any one of the above embodiments, which isrelatively soft to touch.[78.] The thin film of any one of the above embodiments, having achewable configuration.[79.] The thin film of any one of the above embodiments, having aresilient configuration.[80.] The thin film of any one of the above embodiments, having anelastic or malleable configuration.[81.] The thin film of any one of the above embodiments, including aductile property.[82.] The thin film of any one of the above embodiments, furtherincluding a bitter blocker.[83.] The thin film of any one of the above embodiments, furtherincluding a powder coating present on at least one external surface ofthe thin film.[84.] The thin film of any one of the above embodiments, furtherincluding a powder coating present on two opposing external surfaces ofthe thin film.[85.] The thin film of any one of embodiments [83]-[84], wherein thepowder coating includes at least one of talc and microcrystallinecellulose.[86.] A thin film that includes:

(a) about 2-24 wt. % solvent,

(b) about 4-50 wt. % binder,

(c) about 0-10 wt. % flavoring agent,

(d) about 1-40 wt. % sweetener,

(e) about 4-22 wt. % lipid,

(f) about 3-22 wt. % emulsifier,

(g) about 0-1.0 wt. % dye or pigment,

(h) about 0-0.1 wt. % preservative,

(i) up to about 65 wt. % active ingredient, and

(j) about 0-20 wt. % powder coating.

[87.] A thin film that includes:

(a) solvent including water,

(b) binder including pectin,

(c) optionally a lipid including at least one of deodorized cocoa butteroil, fruit seed oil, and vegetable based oil.

(d) emulsifier including at least one of glycerin, ethoxylatedmonoglycerides, and ethoxylated diglycerides,

(e) botanical extract,

(f) flavoring agent including mint flavoring

(g) sweetener including at least one of sucralose and acesulfamepotassium,

(h) dye or pigment including at least one of FD&C red, FD&C blue, andFD&C yellow,

(i) a powder coating on at least one external surface, including atleast one of talc, microcrystalline cellulose, mint flavoring,sucralose, acesulfame potassium, and tapioca starch, and

(j) optionally a preservative including at least one of sodium benzoate,methyl paraben, propyl paraben, and sodium sorbate.

[88.] A method of preparing a thin film, the method includes:

(a) mixing a lipid (optional), emulsifier, and solvent to provide auniform first mixture;

(b) contacting an active ingredient with the uniform first mixture toprovide a thickened second mixture;

(c) contacting a binder with the thickened second mixture to provide aslurry; and

(d) hot extruding, casting, and condensing the slurry to provide thethin film; or cooling, shearing, mixing, casting, and condensing theslurry to provide the thin film.

[89.] The method of the above embodiment, wherein the thin film obtainedis a thin film as described in any one of the above embodiments (e.g.,any one of embodiments [1]-[87]).[90.] The method of any one of the above embodiments, wherein the mixingincludes blending.[91.] The method of any one of the above embodiments, wherein the mixingis carried out at a temperature of about 130-140° F. (54.4-60° C.).[92.] The method of any one of the above embodiments, wherein thecontacting of the active ingredient with the uniform first mixturefurther includes contacting at least one of a sweetener, flavoringagent, and dye or pigment with the uniform first mixture.[93.] The method of any one of the above embodiments, wherein thecontacting of the binder with the thickened second mixture includesinitially contacting a non-sticky binder with the thickened secondmixture, and subsequently contacting a sticky binder with the thickenedsecond mixture.[94.] The method of any one of the above embodiments, wherein thecontacting of the binder with the thickened second mixture includesinitially contacting microcrystalline cellulose with the thickenedsecond mixture, and subsequently contacting pectin with the thickenedsecond mixture.[95.] The method of any one of the above embodiments, wherein thecondensing includes heating at a temperature of at least about 50° F.(10° C.).[96.] The method of any one of the above embodiments, wherein thecondensing is carried out for at least about 10 minutes.[97.] The method of any one of the above embodiments, wherein thecondensing includes heating with passive convection.[98.] The method of any one of the above embodiments, wherein thecondensing includes heating with active convection.[99.] The method of any one of the above embodiments, wherein thecondensing is carried out in vacuo.[100.] The method of any one of the above embodiments, further includingcontacting a powder coating with at least one external surface of thethin film.[101.] The method of any one of the above embodiments, further includingcontacting a powder coating with two opposing external sides of the thinfilm.[102.] The method of any one of embodiments [88]-[101], wherein thepowder coating includes at least one of talc and microcrystallinecellulose.[103.] A system that includes:

(a) multiple thin films, each in direct contact with at least one otherthin film, and each independently described in any one of the aboveembodiments (e.g., any one of embodiments [1]-[87]);

(b) packaging material enclosing the multiple thin films; and

(c) printed indicia located on the packaging material;

wherein the multiple thin films do not readily stick to another.[104.] The system of the above embodiment, including at least about 5thin films.[105.] The system of any one of the above embodiments, including up toabout 25 thin films.[106.] The system of any one of the above embodiments, wherein each ofthe multiple thin films independently has a dimension of 23 mm×38 mm, ±3mm.[107.] The system of any one of the above embodiments, wherein each ofthe multiple thin films is independently prepared as described in anyone of the above embodiments (e.g., any one of embodiments [88]-[102]).

The invention will now be described by the following non-limitingexamples.

EXAMPLES Example 1 Preparation of Thin Film with an Encapsulated ActiveIngredient

Liposomes can be prepared by using a phospholipid like hydroxylatedlecithin, an oil such as deodorized cocoa butter, water, and glycerin.These substances are mixed (warm), so the cocoa butter is melted, usinga high shear blender or a hand-held mixer. To this is added the activeingredient, whether they are water-soluble or fat-soluble. A high shearblender can be employed. The active ingredient can be incorporated intothe layers of the forming liposomes. After the formation of the activeimpregnated liposomes, the following substances can be added:flavorings, sweeteners, colors, non-sticky binders (e.g.,microcrystalline cellulose), and finally a sticky binder (e.g., pectin).This slurry is now a colloid consisting of liposomes dispersed in anaqueous hydrogel.

The slurries are typically 60-80% water. They can be spread onto glassin the laboratory or onto PET (polyethylene terephthalate) film in thefactory and cooked at 60-105° C. both in laboratory and factorysettings. The slurries can be hardened into flexible films that are4-22% water when cooking is complete. Further cooking leads to brittleand eventually charred products. Laboratory films are typically cut andpackaged as soon as they are out of the oven. The hardened films fromthe factory are cured for 1-4 days then slit, cut, and packaged. Thefilms cannot be over-cured, so sometimes longer cure times happen due totime and availability of working staff. Driving off of water from a warmand pliable slurry is believed to yield metamorphosed liposomalstructures now suspended in close proximity in a solid wafer film.Curing completes the metamorphosis. Without being bound to anyparticular theory, there is believed to be a plurality of liposomalstructures, and even multilayer lipid bilayer sheets in the finalproducts.

Example 2 Exemplary Formulations, Oral Thin Film

Ingredient Amount present Amount present Amount present solvent 2-24 wt.% 4-12 wt. % 8 wt. % binder 4-50 wt. % 10-36 wt. % 25 wt. % flavoringagent 0-10 wt. % 2-4 wt. % 4 wt. % sweetener 0-40 wt. % 6-14 wt. % 9.5wt. % lipid 0-22 wt. % 10-18 wt. % 14.8 wt. % emulsifier 3-22 wt. % 8-18wt. % 14 wt. % dye or pigment 0-1.0 wt. % 0.01-0.04 wt. % 0.02 wt. %preservative 0-0.1 wt. % 0-0.02 wt. % 0 wt. % active up to wt. % up towt. % about 33 wt. % ingredient: about 65 about 40 botanical extractpowder coating 0-20 wt. % 5-15 wt. % 10 wt. % Note: In the aboveformulations, the finished product may include about 8-10 wt. %moisture.

Example 3 Exemplary Formulations, Oral Thin Film

Ingredient Amount present Amount present Amount present water 2-24 wt. %4-12 wt. % 8 wt. % pectin and microcrystalline 4-50 wt. % 10-36 wt. % 25wt. % cellulose mint flavoring 0-10 wt. % 2-4 wt. % 4 wt. % sucralose,acesulfame 0-40 wt. % 6-14 wt. % 9.5 wt. % potassium, and/or ammoniumglycyrrhizinate hydroxylated lecithin, 0-22 wt. % 10-18 wt. % 14.8 wt. %deodorized cocoa butter, fruit seed oil, and/or vegetable based oilglycerin, ethoxylated 3-22 wt. % 8-18 wt. % 14 wt. % monoglycerides,and/or ethoxylated diglycerides FD&C food colorings 0-1.0 wt. %0.01-0.04 wt. % 0.02 wt. % sodium benzoate 0-0.1 wt. % 0-0.02 wt. % 0wt. % active ingredient: botanical up to about 65 wt. % up to about 40wt. % about 33 wt. % extract powder coating of talc, 0-20 wt. % 5-15 wt.% 10 wt. % microcrystalline cellulose, powdered flavoring, and/orsweetener Note: In the above formulations, the finished product mayinclude about 8-10 wt. % moisture.

Example 4 Oral Dissolvable Film Containing Kavalactones

The goal of this procedure is to produce a 38 mm×23 mm, 120 mg totalweight film, containing 18 mg of kavalactones botanical extract.

This mixture used a total of 356 mL water. The water was heated in a 400mL polypropylene beaker in a microwave oven to about 60° C.

To a mass of 18.5 g of glycerin, 5.08 g of hydroxylated soy lecithin,and 5.64 g of deodorized cocoa butter in a 100 mL glass beaker was added40 mL of 60° C. water. The mixture was stirred with a metal spatulauntil the cocoa butter was fully melted and the contents are uniformlymixed (about 1-2 minutes). This mixture was poured into a blender. Thebeaker was rinsed with 80 mL, 60° C. water. This rinse water was pouredinto the mixture in the blender. The remainder of the hot water wasadded to the blender.

With stirring on low, 18.5 g of 75% kavalactones (previously extractedfrom kava roots using supercritical carbon dioxide) was added. Afterstirring on a low setting, about 1 minute, the ingredients werethoroughly mixed and distributed. With mixing, the following ingredientswere added in order: 3.70 g A.M. Todd's Crystal White®, 5.54 gsucralose, 2.77 g acesulfame potassium, 3.70 g 50 μm microcrystallinecellulose, and 12 mg FD&C blue #1. In a rapid fashion, over about 5-10seconds, is added 29.0 g C.P. Kelco's Slow Set Genu® Pectin. The mixturewas stirred from low to high speeds until smooth, or for about 3minutes.

The slurry from above was spread onto 12 inch×16 inch tempered glassplates using a ⅝ inch diameter glass rod with 17 gauge Nichrome wiredepth gauges. The plates were cooked in a 70° C. convection oven forabout 20 minutes. Upon removal, the plates were cooled and the film wascut using a razorblade and stainless steel cutting templates to yield 38mm×23 mm strips that weigh about 120 mg each.

Example 5 Oral Dissolvable Film Containing Kavalactones, CBD, and THC

The goal of this pro-cedure was to produce a 38 mm×23 mm, 120 mg totalweight film, containing 18 mg of kavalactones, 5 mg industrialhemp-derived cannabidiol (CBD), and 1.7 mg industrial hemp-derivedtetrahydrocannabinol (THC) botanical extracts.

This mixture will used a total of 230 mL water. The water was heated ina 400 mL poly-propylene beaker in a microwave oven to about 60° C.

To a mass of 18.0 g glycerin, 5.50 g hydroxylated lecithin, and 6.10 gCaptex® 355 (medium chain fractionated coconut oil) in a 100 mL glassbeaker was added 40 mL of 60° C. water. The mixture was stirred with ametal spatula until the materials are evenly disbursed (30-60 seconds).The mixture was poured into a 1 L stainless steel solid flatwarecylinder. The beaker was rinsed with 80 mL, 60° C. water. This rinsewater was poured into the mixture in the stainless steel solid flatwarecylinder. The remainder of the hot water was added to the stainlesssteel solid flatware cylinder.

To the mixture was added 20.0 g of 75% kavalactones (previouslyextracted from kava roots using supercritical carbon dioxide). Themixture was stirred with a with a handheld, high-shear mixer until themixture was homogenous. To the mixture was added 7.38 g of industrialhemp botanical extract that is 56.44% CBD, 19.65% THC. The mixture wasfurther stirred with a with a handheld, high-shear mixer for about 1minute until the ingredients were thoroughly mixed and distributed. Withmixing, the following ingredients were added in order: 4.00 g A.M.Todd's Crystal White®, 6.00 g sucralose, 3.00 g acesulfame potassium(ACE-K), and 4.00 g 50 μm microcrystalline cellulose. In a rapidfashion, over about 5-10 seconds, was added 26.0 g C.P. Kelco's Slow SetGenu® Pectin. The mixture was stirred with a with a handheld, high-shearmixer until smooth, or for about 3 minutes.

The slurry was then spread onto glass plates using a 12×16 inch temperedglass sheet and a glass rod fitted with 18 gauge Nichrome wire depthgauges. The plates were cooked in a convection oven for about 15 minutesat 70° C. The film was cut using templates and razor blade. Theindividual film doses were separated from the glass plates with a razorblade.

Example 6 Oral Dissolvable Film, Lipid Free, Containing Kavalactones,CBD, and THC

The goal of this procedure was to produce a 38 mm×23 mm, 140 mg totalweight film, containing 18 mg of kavalactones, 5.0 mg industrialhemp-derived cannabidiol (CBD), and 1.7 mg industrial hemp-derivedtetrahydrocannabinol (THC) botanical extracts.

This mixture used a total of 220 mL water. The water was heated in a 400mL poly-propylene beaker in a microwave oven to about 60° C.

To a mass of 17.0 g glycerin and 19.0 g PEG-1000 in a 100 mL glassbeaker was added 40 mL of 60° C. water. The mixture was stirred with ametal spatula until the materials were evenly disbursed (30-60 seconds).The mixture was poured into a 1 L stainless steel solid flatwarecylinder. The beaker was rinsed with 80 mL, 60° C. water. This rinsewater was poured into the mixture in the stainless steel solid flatwarecylinder. The remainder of the hot water was added to the stainlesssteel solid flatware cylinder.

To the mixture was added 17.1 g of 75% kavalactones (previouslyextracted from kava roots using supercritical carbon dioxide). Themixture was stirred with a with a handheld, high-shear mixer until themixture was homogenous. To the mixture was added 6.33 g of industrialhemp botanical extract that was 56.44% CBD, 19.65% THC. The mixture wasfurther stirred with a with a handheld, high-shear mixer for about 1minute until the ingredients were thoroughly mixed and distributed. Withmixing, the following ingredients were added in order: 4.00 g A.M.Todd's Crystal White®, 6.00 g sucralose, 3.00 g acesulfame potassium(ACE-K), and 3.00 g 50 μm microcrystalline cellulose (FMC's Endurance®).In a rapid fashion, over about 5-10 seconds, was added 24.6 g C.P.Kelco's Slow Set Genu® Pectin. The mixture was stirred with a with ahandheld, high-shear mixer until smooth, or for about 3 minutes.

The slurry was then spread onto glass plates using a 12×16 inch temperedglass sheet and a glass rod fitted with 18 gauge Nichrome wire depthgauges. The plates were cooked in a convection oven for about 15 minutesat 70° C. The film was cut using templates and razor blade. Theindividual film doses were separated from the glass plates with a razorblade.

What is claimed is:
 1. An oral dissolvable film comprising: (a) solvent,(b) binder, (c) optionally a lipid, (d) emulsifier, (e) botanicalextract, (f) optionally a dough conditioner, (g) optionally a flavoringagent, (h) optionally a sweetener, (i) optionally a dye or pigment, (j)a powder coating on at least one external surface, and (k) optionally apreservative.
 2. The oral dissolvable film of claim 1, wherein thebotanical extract comprises less than about 1 wt. % plant waxes.
 3. Theoral dissolvable film of claim 1, wherein the botanical extractcomprises less than about 1 wt. % plant lipids.
 4. The oral dissolvablefilm of claim 1, wherein the botanical extract comprises less than about1 wt. % plant pigments.
 5. The oral dissolvable film of claim 1, whereinthe botanical extract comprises less than about 1 wt. % chlorophylls. 6.The oral dissolvable film of claim 1, wherein the botanical extractcomprises at least about 70 wt. % in the aggregate of kavalactones,tetrahydrocannabinols (THCs), cannabidiol (CBD), and cannabinoids. 7.The oral dissolvable film of claim 1, wherein at least about 50 wt. % ofthe botanical extract is encapsulated by the lipid.
 8. The oraldissolvable film of claim 1, wherein the botanical extract is present inat least about 20 wt. % of the thin film.
 9. The oral dissolvable filmof claim 1, configured and formulated for the immediate release (IR) ofat least one of kavalactones, tetrahydrocannabinols (THCs), cannabidiol(CBD), and cannabinoids.
 10. The oral dissolvable film of claim 1,configured and formulated for the sustained release (SR), delayedrelease (DR), modified release (MR), extended release (XR), orcontrolled release (CR) of at least one of kavalactones,tetrahydrocannabinols (THCs), cannabidiol (CBD), and cannabinoids. 11.The oral dissolvable film of claim 1, wherein the dough conditionercomprises at least one of glycerin, ethoxylated monoglycerides, andethoxylated diglycerides.
 12. An orally dissolving film comprising: (a)solvent comprising water, (b) binder comprising pectin, (c) optionally alipid comprising at least one of deodorized cocoa butter oil, fruit seedoil, and vegetable based oil, (d) emulsifier comprising at least one ofglycerin, ethoxylated monoglycerides, and ethoxylated diglycerides, (e)botanical extract, (f) flavoring agent comprising mint flavoring (g)sweetener comprising at least one of sucralose and acesulfame potassium,(h) dye or pigment comprising at least one of FD&C red, FD&C blue, andFD&C yellow, (i) a powder coating on at least one external surface,comprising at least one of talc, microcrystalline cellulose, mintflavoring, sucralose, acesulfame potassium, and tapioca starch, and (j)optionally a preservative comprising at least one of sodium benzoate,methyl paraben, propyl paraben, and sodium sorbate.
 13. The orallydissolving film of claim 12, wherein the botanical extract comprisesless than about 1 wt. % plant waxes.
 14. The orally dissolving film ofclaim 12, wherein the botanical extract comprises less than about 1 wt.% plant lipids.
 15. The orally dissolving film of claim 12, wherein thebotanical extract comprises less than about 1 wt. % plant pigments. 16.The orally dissolving film of claim 12, wherein the botanical extractcomprises less than about 1 wt. % chlorophylls.
 17. The orallydissolving film of claim 12, wherein the botanical extract comprises atleast about 70 wt. % in the aggregate of kavalactones,tetrahydrocannabinols (THCs), cannabidiol (CBD), and cannabinoids. 18.The orally dissolving film of claim 12, wherein at least about 50 wt. %of the botanical extract is encapsulated by the lipid.
 19. The orallydissolving film of claim 12, wherein the botanical extract is present inat least about 20 wt. % of the thin film.
 20. The orally dissolving thinof claim 12, configured and formulated for the immediate release of atleast one of kavalactones, tetrahydrocannabinols (THCs), cannabidiol(CBD), and cannabinoids.
 21. The orally dissolving film of claim 12,configured and formulated for the sustained release (SR), delayedrelease (DR), modified release (MR), extended release (XR), orcontrolled release (CR) of at least one of kavalactones,tetrahydrocannabinols (THCs), cannabidiol (CBD), and cannabinoids. 22.The orally dissolving film of claim 12, wherein the dough conditionercomprises at least one of glycerin, ethoxylated monoglycerides, andethoxylated diglycerides.